Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University, Grudziadzka 5, 87-100, Torun, Poland.
Sci Rep. 2019 Dec 12;9(1):18974. doi: 10.1038/s41598-019-55461-8.
Reelin is a large glycoprotein controlling brain development and cell adhesion. It regulates the positioning of neurons, as well as neurotransmission and memory formation. Perturbations in reelin signaling are linked to psychiatric disorders. Reelin participates in signal transduction by binding to the lipoprotein receptors VLDLR and ApoER2 through its central region. This part is rich in repeating BNR-EGF-BNR modules. We used standard molecular dynamics, steered molecular dynamics, and perturbation response scanning computational methods to characterize unique dynamical properties of reelin modules involved in signaling. Each module has specific sensors and effectors arranged in a similar topology. In the modules studied, disulfide bridges play a protective role, probably making both selective binding and protease activity of reelin possible. Results of single reelin molecule stretching by atomic force microscopy provide the first data on the mechanical stability of individual reelin domains. The forces required for partial unfolding of the modules studied are below 60 pN.
Reelin 是一种控制大脑发育和细胞黏附的大型糖蛋白。它调节神经元的定位，以及神经递质传递和记忆形成。 Reelin 信号转导的紊乱与精神疾病有关。 Reelin 通过其中心区域与脂蛋白受体 VLDLR 和 ApoER2 结合参与信号转导。该部分富含重复的 BNR-EGF-BNR 模块。我们使用标准分子动力学、导向分子动力学和扰动响应扫描计算方法来表征参与信号转导的 Reelin 模块的独特动力学特性。每个模块都有特定的传感器和效应器，以相似的拓扑结构排列。在研究的模块中，二硫键起着保护作用，可能使 Reelin 的选择性结合和蛋白酶活性成为可能。原子力显微镜对单个 Reelin 分子拉伸的结果提供了关于单个 Reelin 结构域机械稳定性的第一个数据。研究模块部分展开所需的力低于 60 pN。
